[unreadable] The molecular and cellular basis for certain aspects of drug addiction is becoming well established. Researchers understand a great deal about how drugs operate at their primary targets, as well as how they bring about long-term cellular, molecular, and behavioral alterations. Noticeably missing, however, are effective treatments for addicted individuals. The challenge is to understand why relapse is so prevalent. One posited explanation for the high rates of relapse is the conditioning of effects of drugs. Drug-associated cues can evoke strong cravings in former drug users, and can be a powerful determinant of relapse to drug use. While this behavior is well characterized, very little is known about the cellular and molecular bases for drug-associated conditioned behavior. The proposed research will investigate the gene regulatory and signal transduction mechanisms involved in the expression of conditioned responses to an environment that had previously, repeatedly been paired with administration of morphine or nicotine, as well as how these relate to extinction of the conditioned responses. The guiding notion is that a better understanding of the basic cellular processes at work during the expression of drug-associated conditioned responses may lead to better treatments for addicted individuals. [unreadable] [unreadable] [unreadable] [unreadable]